FDA Expands Use of HCV Drug Daclatasvir (Daklinza )

Megan Brooks

February 09, 2016

The US Food and Drug Administration (FDA) has approved expanded use of the NS5A replication complex inhibitor daclatasvir (Daklinza, Bristol-Myers Squibb) for hepatitis C virus (HCV) infection.

The drug can now be used in combination with sofosbuvir (Sovaldi, Gilead Sciences), with or without ribavirin, to treat patients with HCV genotypes 1 and 3, the company said in a news release.

The FDA first approved daclatasvir for treatment of chronic HCV genotype 3 in July 2015, as reported by Medscape Medical News.

"The expanded indication for Daklinza offers an additional treatment option for multiple subsets of patients who have genotype 1 or 3 chronic HCV," Chris Boerner, head of US Commercial, Bristol-Myers Squibb, said in a company news release.

The expanded label includes three additional "challenging-to-treat" patient populations — those with HCV and HIV-1 coinfection, advanced cirrhosis, or recurrence of HCV after liver transplant, the release notes. "HCV/HIV-coinfected patients and patients with advanced cirrhosis or post-transplant recurrence of HCV still pose a treatment challenge to physicians," Boerner added.

The efficacy and safety of daclatasvir-containing regimens were demonstrated in the ALLY-1 and ALLY-2 phase 3 clinical trials.

The ALLY-2 trial included 153 treatment-naïve and treatment-experienced HCV/HIV-coinfected patients treated with daclatasvir plus sofosbuvir for 12 weeks. The primary endpoint was sustained virologic response at week 12 (SVR12) in genotype 1 treatment-naïve patients.

SVR12 rates were "high" regardless of baseline subgroup, including Black/African American (98% in all genotypes studied), and high baseline viral load (≥ 6,000,000 IU/mL) (97% in all genotypes studied), the company said.

SVR12 rates were also similar in patients on highly active antiretroviral therapy (HAART) regimens, which included protease inhibitors (97% in all genotypes), non-nucleoside reverse transcriptase inhibitors (100% in all genotypes), and integrase inhibitors (95% in all genotypes), they point out.

There were no treatment-related serious adverse events, and no patient discontinued treatment due to adverse events (AEs). The most common treatment-related AEs were fatigue (15%), nausea (9%), headache (8%), and diarrhea (7%).

The ALLY-1 trial included 113 patients with chronic HCV infection and Child-Pugh A, B, or C advanced cirrhosis or HCV recurrence after liver transplant treated with daclatasvir plus sofosbuvir with ribavirin for 12 weeks. SVR12 rates were similar between genotype 3 (5/6 with Child-Pugh B or C cirrhosis and 10/11 post-liver transplant) and genotype 1 subjects with or without decompensated cirrhosis, the company said.

The ALLY-1 and ALLY-2 trials showed that daclatasvir can be given alongside the most commonly used HIV medications and post-transplant immunosuppressive regimens, the company noted in their news release.

"Based on the drug-drug interaction profile, there is no need to change or adjust HAART regimens, including darunavir-ritonavir, atazanavir-ritonavir, lopinavir-ritonavir, efavirenz, raltegravir, dolutegravir, nevirapine and rilpivirine," they point out. "The dose of Daklinza was adjusted for some HAART regimens. Daklinza is also compatible with many immunosuppressive regimens, with no treatment-limiting drug-drug interactions. The ALLY-1 trial studied most immunosuppressants: cyclosporine, tacrolimus, sirolimus, everolimus, corticosteroids, or mycophenolate mofetil."

Full prescribing information for daclatasvir is available here.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.